The Red Edge: Bilin-Binding Photoreceptors as Optogenetic Tools and Fluorescence Reporters

This review adds the bilin-binding phytochromes to the Chemical Reviews
thematic issue “Optogenetics and Photopharmacology”. The work is structured into two
parts. We first outline the photochemistry of the covalently bound tetrapyrrole
chromophore and summarize relevant spectroscopic, kinetic, biochemical, and physiological
properties of the different families of phytochromes. Based on this knowledge, we then
describe the engineering of phytochromes to further improve these chromoproteins as
photoswitches and review their employment in an ever-growing number of different
optogenetic applications. Most applications rely on the light-controlled complex formation
between the plant photoreceptor PhyB and phytochrome-interacting factors (PIFs) or C-
terminal light-regulated domains with enzymatic functions present in many bacterial and
algal phytochromes. Phytochrome-based optogenetic tools are currently implemented in bacteria, yeast, plants, and animals to
achieve light control of a wide range of biological activities. These cover the regulation of gene expression, protein transport into cell organelles, and the recruitment of phytochrome- or PIF-tagged proteins to membranes and other cellular compartments. This compilation illustrates the intrinsic advantages of phytochromes compared to other photoreceptor classes, e.g., their bidirectional dual-wavelength control enabling instant ON and OFF regulation. In particular, the long wavelength range of absorption and fluorescence within the “transparent window” makes phytochromes attractive for complex applications requiring deep tissue penetration or dual-wavelength control in combination with blue and UV light-sensing photoreceptors. In addition to the wide variability of applications employing natural and engineered phytochromes, we also discuss recent progress in the development of bilin-based fluorescent proteins.